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Journal of Protein Chemistry

, Volume 13, Issue 4, pp 375–380 | Cite as

Prediction of conformation of rat galanin in the presence and absence of water with the use of monte Carlo methods and the ECEPP/3 force field

  • A. Liwo
  • S. Ołdziej
  • J. Ciarkowski
  • G. Kupryszewski
  • M. R. Pincus
  • R. J. Wawak
  • S. Rackovsky
  • H. A. Scheraga
Article

Abstract

The conformation of the 29-residue rat galanin neuropeptide was studied using the Monte Carlo with energy minimization (MCM) and electrostatically driven Monte Carlo (EDMC) methods. According to a previously elaborated procedure, the polypeptide chain was first treated in a united-residue approximation, in order to enable extensive exploration of the conformational space to be carried out (with the use of MCM), Then the low-energy united-residue conformations were converted to the all-atom representations, and EDMC simulations were carried out for the all-atom polypeptide chains, using the ECEPP/3 force field with hydration included. In order to estimate the effect of environment on galanin conformation, the low-energy conformations obtained as a result of these simulations were taken as starting structures for further EDMC runs that did not include hydration. The lowest-energy conformation obtained in aqueous solution calculations had a nonhelical N-terminal part packed against the nonpolar face of a residual helix that extended from Pro13 toward the C-terminus. One next lowest-energy structure was a nearly-all-helical conformation, but with a markedly higher energy. In contrast, all of the low-energy conformations in the absence of water were all-helical differing only by the extent to which the helix was kinked around Pro13. These results are in qualitative agreement with the available NMR and CD data of galanin in aqueous and nonaqueous solvents.

Key words

Rat galanin conformational energy calculations Monte Carlo methods effect of environment on conformation 

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References

  1. Ahrén, B., Arkhammar, P., Berggren, P. O., and Nilsson, T. (1986).Biochem. Biophys. Res. Commun. 140, 1059–1063.PubMedGoogle Scholar
  2. Anfinsen, C. B. (1973).Science 181, 223–230.PubMedGoogle Scholar
  3. Bauer, F. E., Ginsberg, L., Venetikou, M., MacKay, D. J., Burrin, J. M., and Bloom, S. R. (1986).Lancet 2, 192–194.PubMedGoogle Scholar
  4. Bersani, M., Johnsen, A. H., Hojrup, P., Dunning, B. E., Andreasen, J. J., and Holst, J. J. (1991).FEBS Lett. 283, 189–194.PubMedGoogle Scholar
  5. Crawley, J. N., Austin, M. C., Fiske, S. M., Martin, B., Consolo, S., Berthold, M., Langel, U., Fisone, G., and Bartfai, T. (1990).J. Neurosci. 10, 3695–3700.PubMedGoogle Scholar
  6. De Loof, H., Nilsson, L., and Rigler, R. (1992).J. Am. Chem. Soc. 114, 4028–4035.Google Scholar
  7. Fisone, G., Wu, C. F., Consolo, S., Nordström, Ö., Brynne, N., Bartfai, T., Melander, T., and Hökfelt, T. (1987).Proc. Natl. Acad. Sci. USA 84, 7339–7343.PubMedGoogle Scholar
  8. Fisone, G., Berthold, M., Bedecs, K., Unden, A., Bartfai, T., Bertorelli, R., Consolo, S., Crawley, J., Martin, B., Nilson, S., and Hökfelt, T. (1989).Proc. Natl. Acad. Sci. USA 86, 9588–9591.PubMedGoogle Scholar
  9. Hökfelt, T., Millhorn, D., Seroogy, K., Tsuruo, Y., Ceccatelli, S., Lindh, B., Meister, B., Mealander, T., Schalling, M., Bartfai, T., and Terenius, L. (1987).Experientia 43, 768–780.PubMedGoogle Scholar
  10. Land, T., Langel, U., Low, M., Berthold, M., Unden, A., and Bartfai, T. (1991).Int. J. Peptide Protein Res. 38, 267–272.Google Scholar
  11. Lagny-Pourmir, I., Lorinet, A. M., Yanaihara, N., and Laburthe, M. (1989).Peptides 10, 757–761.PubMedGoogle Scholar
  12. Li, Z., and Scheraga, H. A. (1987).Proc. Natl. Acad. Sci. USA 84, 6611–6615.PubMedGoogle Scholar
  13. Li, Z., and Scheraga, H. A. (1988).J. Mol. Struct. (Theochem.) 179, 333–352.Google Scholar
  14. Liwo, A., Pincus, M. R., Wawak, R. J., Rackovsky, S., and Scheraga, H. A. (1993a).Protein Sci. 2, 1697–1714.PubMedGoogle Scholar
  15. Liwo, A., Pincus, M. R., Wawak, R. J., Rackovsky, S., and Scheraga, H. A. (1993b).Protein Sci. 2, 1715–1731.PubMedGoogle Scholar
  16. Némethy, G., Gibson, K. D., Palmer, K. A., Yoon, C. N., Paterlini, G., Zagari, A., Rumsey, S., and Scheraga, H. A. (1992).J. Phys. Chem. 96, 6472–6484.Google Scholar
  17. Rattan, S. (1991).Gastroenterology 100, 1762–1768.PubMedGoogle Scholar
  18. Rekowski, P., Kupryszewski, G., Łubkowski, J., Ołdziej, S., Wiczk, W., and Liwo, A. (1993).Biophs. Chem. (submitted).Google Scholar
  19. Rigler, R., Wennerberg, A., Cooke, R. M., Elofsson, A., Nilsson, L., Vogel, H., Holley, L. H., Carlquist, M., Langel, U., Bartfai, T., and Campbell, I. D. (1991). InGalanin (Hökfelt, T., and Bartfai, T., eds.) Macmillan, New York, pp. 17–25.Google Scholar
  20. Rippoll, D. R., and Scheraga, H. A. (1988)Biopolymers 27, 1283–1303.PubMedGoogle Scholar
  21. Rippoll, D. R., and Scheraga, H. A. (1990).Biopolymers 30, 165–176.PubMedGoogle Scholar
  22. Rökaeus, Å., and Carquist, M. (1988).FEBS Lett. 234, 400–406.PubMedGoogle Scholar
  23. Scheraga, H. A. (1989).Chemica Scripta 29A, 3–13.Google Scholar
  24. Späth, H. (1980). Cluster Analysis Algorithms. Halsted Press, New York, pp. 170–194.Google Scholar
  25. Tatemoto, K., Rökaeus, Å., Jörnvall, H., McDonald, T. J., and Mutt, V. (1983).FEBS Lett. 164, 124–128.PubMedGoogle Scholar
  26. Vila, J., Williams, R. L., Vásquez, M., and Scheraga, H. A. (1991).Proteins: Struct. Func. Genet. 10, 199–218.Google Scholar
  27. Vrontakis, M. E., Peden, L. M., Duckworth, M. L., and Friesen, H. G. (1987).J. Biol. Chem. 262, 16755–16758.PubMedGoogle Scholar
  28. Wennerberg, A., Cooke, R. M., Carlquist, M., Rigler, R., and Campbell, I. D. (1990).Biochem. Biophys. Res. Commun. 166, 1102–1109.PubMedGoogle Scholar
  29. Wiesenfeld-Hallin, Z., Xu, X.-J., Villar, M. J., and Hökfelt, T. (1990).Neurosci. Lett. 109, 217–221.PubMedGoogle Scholar
  30. Williams, R. L., Vila, J., Perrot, G., and Scheraga, H. A. (1992).Proteins: Struct. Funct. Genet. 14, 110–119.Google Scholar
  31. Xu, X.-J., Wiesenfeld-Hallin, Z., Fisone, G., Bartfai, T., and Hökfelt, T. (1990).Eur. J. Pharmacol. 182, 137–141.PubMedGoogle Scholar
  32. Zimmermann, S. S., Pottle, M. S., Némethy, G., and Scheraga, H. A. (1977).Macromolecules 10, 1–9.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • A. Liwo
    • 1
  • S. Ołdziej
    • 1
  • J. Ciarkowski
    • 1
  • G. Kupryszewski
    • 1
  • M. R. Pincus
    • 2
  • R. J. Wawak
    • 3
  • S. Rackovsky
    • 4
  • H. A. Scheraga
    • 3
  1. 1.Department of ChemistryUniversity of GdańskGdańskPoland
  2. 2.Department of Pathology, Division of Clinical PathologyState University of New York, Health Science CenterSyracuse
  3. 3.Baker Laboratory of ChemistryCornell UniversityIthaca
  4. 4.Department of Biophysics, School of Medicine and DentistryUniversity of RochesterRochester

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